Transforming growth factor beta (TGF-B) is a family of related multifunctional regulators of cell growth which can affect cellular proliferation and differentiation. Two forms of TGF-B, TGF-B1 and TGF-B2, are, in general, multifunctional cytokines that have potent inhibitory effects on the proliferation and effector responses of mitogen-, lymphokine-, and alloantigen-activated lymphocytes (Kehrl et al, J Exp Med (1986) 163:1037; Ellingsworth et al, Cell Immunol (1988) 114:41-45 in press; Kehrl et al, J Immunol (1986) 137:3855; Ranges et al, J Exp Med (1987) 166:991). In addition, TGF-B1 and TGF-B2 affect the proliferation and differentiation of other cells of the immune system including macrophages (Wahl et al, Proc Natl Acad Sci USA (1987) 84:5788), pre-B cells (Lee et al, J Exp Med (1987) 166:1290), hematopoietic stem cells (Ohta et al, Nature (1987) 329:539; Ishibashi et al, Blood (1987) 69:1737; Keller et al, J Exp Med (1988) in press 168:737-750; Sing et al, Blood (1988) in press), and NK cells (Rook et al, J Immunol (1986) 136:3916).
The generation of immunoprecipitating and neutralizing antibodies to native TGF-B has been extremely difficult due to the highly conserved nature of native TGF-B among different species. The human sequence of TGF-B1 is identical to the bovine and porcine sequences and differs from the murine sequence by one amino acid- TGF-B1 is a dimer composed of two identical disulfide-linked chains of 112 amino acid residues.
TGF-B2 is also a dimeric polypeptide and is disclosed in U.S. Pat. No. 4,774,322, filed 10 December 1987, assigned to Collagen Corporation. Even though there are 14 amino acid differences in the first 36 amino acids residues of the two forms, their biological activities are similar (Cheifetz et al, Cell (1987) 48:409-415; Seyedin et al, J Biol Chem (1987) 262:1946-1949).
Western blots and immunohistochemical localization studies on TGF-B1 have been performed using a polyclonal rabbit antiserum obtained by immunization with a synthetic peptide corresponding to the NH.sub.2 -terminal 30 amino acids of TGF-B1 (Ellingsworth et al, J Biol Chem (1986) 261:12362). Polyclonal antisera to human and porcine TGF-B (Keski-Oja et al, Cancer Res (1987) 47:6451-6458) and to porcine TGF-B2 (Rosa et al, Science (1988) 239:783-785) have been shown to neutralize the biological activity of TGF-B1 and TGF-B2, respectively. Monoclonal antibodies specific to TGF-B have not been previously described. The availability of these specific antibodies is important for characterization of the role played by TGF-B in the immune system and other physiological processes.
Antibodies to TGF-B are needed to investigate the varied biological actions of TGF-B, to study TGF-B biosynthesis, and to determine differences in activity or effect, if any, between the forms of TGF-B. These antibodies would also have therapeutic applications for treating indications where there is an overproduction of TGF-B (e.g., acute liver injury, chronic hepatic fibrosis) and for diagnosing or treating malignancies (e.g., sarcomas and melanomas) and metastatic cancers.